Otitis media is a common disease in children. The term “otitis media” encompasses a number of clinical disorders including myringitis, otitis media with effusion (OME), chronic suppurative otitis media and acute otitis media (AOM) (24). Acute otitis media (AOM) is a symptomatic illness associated with upper respiratory symptoms, pain, fever and otorrhea. It is the most common infectious disease worldwide, leading to excessive antibiotic consumption in children in most countries and to a substantial burden of deafness and other complications in the developing countries (1-3).
AOM is fairly common and about 60-70% of children experience at least one episode of AOM during the first 3 years of their life (4,5). A subpopulation of children experience recurrent otitis media. Those who experience 3 or more episodes of AOM within 6 months or 4 infections within a year are considered otitis-prone, and represent 10-30% of the total population of children (4;5).
Nasopharyngeal (NP) colonization with one or more otopathogens is a necessary precedent to the development of AOM. Streptococcus pneumoniae (Spn), non-typeable Haemophilia influenzae (NTHi) and Moraxella Catarrhalis are the most common otopathogcns causing AOM, and of these three, Spn predominates (6). A direct relationship between frequency of colonization with NTHi and the frequency of AOM has been noted (J. Infect Dis 170:862-866).
Recurrent AOM is currently treated with different antibiotics of escalating strength on the presumption that the recurrent infections are caused by increasingly antibiotic-resistant bacteria. When recurrences occur at a frequency of 3 in 6 months or 4 in 12 months, then tymnpanostomy tube surgery is often performed, with or without concurrent adenoidectomy and/or tonsillectomy.
In regards to prophylactic measures, at present, there are two available types of pneumococcal vaccines. The first includes capsular polysaccharides from 23 types of S. pneumoniae, which together represent the capsular types of about 90% of strains causing pneumococcal infection. This vaccine, however, is not very immunogenic in young children (Fedson, and Musher 2004, “Pneumococcal Polysaccharide Vaccine”, pp. 529-588; In Vaccines. S. A. Plotikin and W. A. Orenstein (eds.), W.B. Saunders and Co., Philadelphia, Pa.; Shapiro et. al., N. Engl. J. Med. 325:1453-1460 (1991)) as they do not generate a good immune response to polysaccharide antigens prior to 2 years of age. This vaccine is not recommended for the prevention of otitis media.
Conjugate vaccines represent the second available type of pneumococcal vaccine. These vaccines which include serotype specific capsular polysaccharide antigens conjugated to a protein carrier, elicit serotype-specific protection. Currently available are 7-valent and 13-valent conjugate vaccines: the 7-valent includes 7 polysaccharide antigens (derived from the capsules of serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) and the 13-valent conjugate includes 13 polysaccharide antigens (derived from the capsules of serotypes 1, 3, 5, 6A, 7F, and 19A, plus those covered by the 7-valent). 9-valent and 11-valent conjugate vaccines have also been developed and each includes serotype-specific polysaccharides in addition to those in the 7-valent serotypes 1 and 5 in the 9-valent and types 3 and 7F in the 11-valent).
There are however limitations to conjugate vaccines. For example, as such vaccines elicit serotype-specific protection, to protect against additional serotypes of Streptococcus pneumoniae including those that dominate in the developing world, additional serotype-specific polysaccharides must be included which increases the difficulty of manufacture (Di Fabio et al., Pediatr. Infect. Dis. J. 20:959-967 (2001); Mulholland, Trop. Med. Int. Health 10:497-500 (2005)). The use of the 7-valent conjugate vaccine has also led to an increase in colonization and disease with strains of capsule types not covered by the polysaccharides included in the vaccine (Bogaert et al., Lancet Infect. Dis. 4:144-154 (2004); Eskola et al., N. Engl. J. Med. 344-403-409 (2001); Mbelle et al., J. Infect. Dis. 180:1171-1176 (1999)). As for pneumococcal otitis media, the available conjugate vaccines do not work as well in protecting against the disease as they do to against invasive disease. In addition, AOM recurrences are still possible following vaccination; for example, the subpopulation of children who are particularly prone to recurrent episodes of AOM, experience a number of recurrences and go on to become otitis prone, despite conjugate immunization.
Therefore, there is still a need for compositions for use in, and methods of, preventing or treating recurring pneumococcal AOM.